Modulating central gain in tinnitus: Changes in nitric oxide synthase in the ventral cochlear nucleus

16Citations
Citations of this article
27Readers
Mendeley users who have this article in their library.

Abstract

A significant challenge in tinnitus research lies in explaining how acoustic insult leads to tinnitus in some individuals, but not others. One possibility is genetic variability in the expression and function of neuromodulators - components of neural signaling that alter the balance of excitation and inhibition in neural circuits. An example is nitric oxide (NO) - a free radical and potent neuromodulator in the mammalian brain - that regulates plasticity via both pre-synaptic and postsynaptic mechanisms. Changes in NO have previously been implicated in tinnitus generation, specifically in the ventral cochlear nucleus (VCN). Here, we examined nitric oxide synthase (NOS) - the enzyme responsible for NO production - in the guinea pig VCN following acoustic trauma. NOS was present in most cell types - including spherical and globular bushy cells, small, medium, and large multipolar cells, and octopus cells - spanning the entire extent of the VCN. The staining pattern was symmetrical in control animals. Unilateral acoustic over-exposure (AOE) resulted in marked asymmetries between ipsilateral and contralateral sides of the VCN in terms of the distribution of NOS across the cochlear nuclei in animals with behavioral evidence of tinnitus: fewer NOS-positive cells and a reduced level of NOS staining was present across the whole extent of the contralateral VCN, relative to the ipsilateral VCN. The asymmetric pattern of NOS-containing cells was observed as early as 1 day after AOE and was also present in some animals at 3, 7, and 21 days after AOE. However, it was not until 8 weeks after AOE, when tinnitus had developed, that asymmetries were significant overall, compared with control animals. Asymmetrical NOS expression was not correlated with shifts in the threshold hearing levels. Variability in NOS expression between animals may represent one underlying difference that can be linked to whether or not tinnitus develops after noise exposure.

Figures

  • FIGURE 1 | Examples of different cell types in the VCN that have been stained for NADPH-diaphorase (A–D) or nNOS immunoreactivity (E–H). (A) Globular bushy cell (GC) and octopus cell (OC), (B) medium multipolar (MM) and globular bushy cell (GC), (C) large multipolar or giant cells (LM), (D) spherical bushy cell (SC), (E) octopus cell (OC) and globular bushy cell (GC), (F) medium multipolar (MM) and globular bushy cells (GC), (G) large multipolar (LM) and medium multipolar cells (MM), (H) spherical bushy
  • FIGURE 3 | Representative coronal sections through PVCN from an animal with behavioral evidence of tinnitus. Sections were stained
  • FIGURE 2 | The spatial distribution of NOS in the VCN. The percentage of NADPH-d-positive neurons from the total population of counted
  • FIGURE 4 | NOS expression in GPs with suspected tinnitus compared with controls. (A) The mean (±SEM) distribution of NADPH-d-stained cells across the VCN in five un-exposed controls, expressed as a percentage of the total population of counted NADPH-d-positive cells, and plotted according to caudal–rostral position. VCNipsi is shown in blue and VCNcontra in red. (B) The mean (±SEM) distribution of NADPH-d-stained cells across the VCN in eight
  • FIGURE 5 | Changes in the ratio of NADPH-d staining density in the 120 darkest cells between VCNipsi and VCNcontra occur in animals with behavioral evidence of tinnitus. Tinnitus brains (n= 8) were significantly
  • FIGURE 7 | Variable NOS asymmetries in numbers of stained cells shown for a range of time-points after AOE. (A) Asymmetries between unilaterally noise-exposed VCNipsi and un-exposed VCNcontra are shown for control (n= 5), AOE+ 1day (n= 5), +3days (n= 5), +7days (n= 3),
  • FIGURE 6 | Comparison of the distributions of cross-sectional area of stained somata in the VCN. Somal size data from VCNipsi (shown in blue) and VCNcontra (shown in red) are displayed for both control (n= 5; solid lines) and tinnitus (n= 8; hashed lines) groups of animals, in 20 µm2 bins.
  • FIGURE 8 | The effects of unilateral hearing loss on asymmetries in the numbers of NADPH-d-stained cells. Hearing threshold shifts for each

References Powered by Scopus

This article is free to access.

Neuronal NADPH diaphorase is a nitric oxide synthase

1919Citations
196Readers
Get full text

Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues

1885Citations
138Readers
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Coomber, B., Kowalkowski, V. L., Berger, J. I., Palmer, A. R., & Wallace, M. N. (2015). Modulating central gain in tinnitus: Changes in nitric oxide synthase in the ventral cochlear nucleus. Frontiers in Neurology, 6(MAR). https://doi.org/10.3389/fneur.2015.00053

Readers over time

‘15‘16‘17‘18‘19‘20‘21‘23‘240481216

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 9

64%

Researcher 3

21%

Professor / Associate Prof. 2

14%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 8

47%

Medicine and Dentistry 4

24%

Psychology 3

18%

Neuroscience 2

12%

Article Metrics

Tooltip
Social Media
Shares, Likes & Comments: 2

Save time finding and organizing research with Mendeley

Sign up for free
0